The overall objective is to evaluate the efficacy of less toxic organoselenium compounds as inhibitors colon carcinogenesis in a well- established laboratory animal model and to understand the modulating effects organoselenium compounds responsible for colon cancer prevention. Initially, the organoselenium compounds synthesized in Laboratory Program #1, which show minimum toxicity will be screened for their potential chemopreventive action using in vivo azoxymethane (AOM)-induced aberrant crypt foci (ACF) assay in F344 rats. Organoselenium compounds showing an inhibItory effect in ACF assay will be tested for their efficacy in colon carcinogenesis in male F344 rats. The efficacy of three dose levels (20, 40, and 80% maximum tolerated dose as determined in Laboratory Program #1) of each test compound on AOM-induced initiation and postinitiation phases of colon carcinogenesis in male F344 rats will be studied. At 5 weeks of age, groups of F344 rats will be fed control diets or experimental diets containing different levels of organoselenium compounds. At 7 weeks of age, groups of rats in each dietary group will be treated with a single s.c. dose of AOM (30 mg/kg body wt.) or vehicle alone. Two days after AOM or vehicle treatment, groups of animals fed the control or experimental diets will be transferred, respectively, to experimental or control diets and continued on this regimen until termination of the study at 36 weeks. All animals will then be sacrificed and histopathological evaluation of colon tumors will be performed. Colon tumor incidence and multiplicity among the dietary groups will be tested by appropriate statistical methods. In order to determine the modulating effects of organoselenium compounds during the initiation and postinitiation phases of colon cancer, the effect of test agents on AOM metabolism and AOM-DNA binding will be studied in Laboratory Program #3. In order to determine whether or not dietary organoselenium compounds modify the colonic cellular events associated with tumor promotion, groups of F344 rats treated with AOM or vehicle and fed the organoselenium compounds will be sacrificed at several time points during the course of the dietary regimen and relevant cellular and molecular events namely protein kinase C, tyrosine protein kinase, 1,2-Sn-diacylglycerol kinase, Se-GSH-Px, and GST, in the colon mucosa and colon tumors (at termination) will be measured. The data on each of these biochemical parameters will be compared among the dietary groups using appropriate statistical methods.